The objectives of this research proposal are to determine (a) how advancing age diminishes fever response, (b) whether the integrity of fever response is related to the integrity of cell-mediated immunity, and (c) whether nutritional factors such as zinc deficiency contribute to blunted fever responses associated with age. Elderly persons have a higher prevalence of infectious diseases and suffer greater morbidity and mortality from infectious complications. Moreover, elderly patients with infections have atypical clinical manifestations of infections, particularly fever. Fever is frequently blunted or absent in the presence of infection in this population. The research proposal attempts to investigate this phenomenon and understand its pathogenetic mechanism. The project will evaluate fever responses in young and old mice by injecting endogenous pyrogen extracted from peritoneal macrophages of young and old mice. The fever responses will also be correlated with in vitro testing of cell-mediated immune functions. Finally, young and old mice will be made zinc deficient and evaluated for fever responses to endogenous pyrogens.